Patent GB-727343-A (GB)
Title: Improvements relating to bactericidal salicylanilides
Filed: 1952-12-23
Abstract: The invention comprises compounds of formula <FORM:0727343/IV (b)/1> wherein Q represents hydrogen or halogen; each X represents either hydrogen, halogen or a methyl group; Y represents hydrogen, halogen or a trifluoromethyl group; and each Z represents either hydrogen or halogen, or also in the case of Z3 a methyl group; whilst at least three halogen or halogen-containing substituents of the type defined must be represented by X1, X2, Y, Z1 and Z2, so that two must be present in one of the pairs X1X2, YZ1, or Z1Z2. The compounds are prepared by reacting an appropriate 2-hydroxy- or 2-acyloxy-benzene-1-carboxylic acid or an acylating derivative thereof (e.g. the corresponding carboxylic acid halides) which may contain a halogen substituent or a methyl group in the 4- or 5-position and/or a halogen substituent in the 3-position with an appropriate 5- or preferably a 4 - halogen - 1 - aminobenzene compound which may contain further halogen substituents or a trifluoromethyl group in the meta-position to the amino group, whilst one ortho-position to the amino group should be free of substituents and the other may be occupied by halogens or a methyl group, and, if necessary, saponifying a 2-acyloxy group to a 2-hydroxy group under mild conditions (e.g. using non-caustic alkalies in aqueous or aqueous-organic solution).  The appropriate 2-hydroxybenzoic acids and halogen-aminobenzene compounds are preferably heated in an inert organic solvent such as toluene, chlorobenzene, nitrobenzene or kerosene with dehydrating agents such as phosphorus trichloride or thionyl chloride, advantageously in presence of small amounts of aluminium chloride.  2-Hydroxybenzene-1-carboxylic acids are preferably salicylic acid, 4-chloro-, 4-bromo-, 5-chloro-, 5-bromo-, 3,5-dichloro-, 3,5-dibromo-, 3,5-di-iodo-, 4,5-dichloro-, 4,5-dibromo-, 4-methyl-5-chloro-, 4-methyl-5-bromo-, and 4-methyl-5-iodo-salicylic acids. Halogenaminobenzenes are preferably 4-chloro-, 4-bromo-, 4-iodo-, 2,4- or 2,5-dichloro, 2,4- or 2,5-dibromo-, 3,4-dichloro-, 3,4-dibromo-, 2,4,5-, 2,3,4- or 3,4,5-trichloro-, 3,4-dichloro-6-methyl-, and 3-trifluoromethyl-4-chloro-aniline. The following compounds are described: 5-chlorosalicylic acid - 31,41 - dichloro - anilide, - 21,31,41 - trichloro - anilide, - 31 - trifluoromethyl - 41 - chloro - anilide, - 31,41 - dibrom - anilide, - 31,41,51 - trichloro - anilide, and - 21, 41, 51 - trichloro - anilide; 4 - chlorosalicylic acid - 31,41 - dichloro - anilide, - 31,41,51 - trichloro - anilide, - 21,41,51 - trichloro - anilide, and - 31 - trifluoromethyl - 41 - chloro - anilide; 3,5 - dichlorosalicylic acid - 21,41,51 - trichloroanilide, - 31,41,51 - trichloro - anilide, - 31 - trifluoromethyl - 41 - chloro - anilide, and -21,31,41-trichloro - anilide; 3,5 - dibromosalicylic acid-31,41 - dichloro - anilide, and - 31,41 - dibromo - anilide; 3,5 - di - iodosalicylic acid - 31,41 - dichloro-anilide, and -31,41,51-trichloro-anilide; 4,5 - dichlorosalicylic acid - 31,41 - dichloro - anilide, - 21,41,51 - trichloro - anilide, - 31,41,51 - trichloro - anilide, - 31 - trifluoromethyl - 41 - chloro - anilide, - 21,41 - dichloro - anilide, -21,51-dichloro - anilide, - 41 - chloro - anilide, - 21,41 - dibromo - anilide, - 41 - bromo - anilide, and - 21,31,41 - trichloro - anilide; 4 - methyl - 5 - chloro - salicylic acid - 31,41 - dichloro - anilide -31,41,51-trichloro-anilide, and -31-trifluoromethyl - 41 - chloro - anilide; 5 - bromosalicylic acid - 31,41 - dichloro - anilide, - 31,41,51 - trichloro-anilide, and -21,31,41-trichloro-anilide; and salicylic acid-31,41,51-trichloro-anilide.  4,5-Dichlorosalicylic acid is prepared by acidifying the product formed by treating the sodium salt of 3,4-dichlorophenol with carbon dioxide under pressure.  2 - Acetoxy - 4,5 - dichlorobenzoic acid is prepared by heating 4,5-dichlorosalicylic acid with acetic anhydride in presence of a trace of a mixture of sulphuric and glacial acetic acids. 4,5-Dichloro-2-acetoxybenzoyl chloride is prepared by stirring 2-acetoxy-4,5-dichlorosalicylic acid with thionyl chloride.ALSO:A bactericidal composition comprises salicylanilides of general formula <FORM:0727343/VI/1> wherein Q represents hydrogen or halogen; each X represents either hydrogen, halogen or a methyl group; Y represents hydrogen, halogen or a trifluoromethyl group; and each Z represents either hydrogen or halogen, or also in the case of Z3 a methyl group; whilst at least three halogen or halogen-containing substituents of the type defined must be represented by X1, X2, Y, Z1 and Z2, so that two must be present in one of the pairs X1 X2 YZ1 or Z1 Z2 in solution in water or ethyl alcohol (for use against mould and rot) or incorporated in cleaning agents, ointment boxes or creams. The following salicylanilides are described: 5-chlorosalicylic acid-31 41-dichloro-anilide, -21 , 31 , 41-trichloro-onilide, -31-trifluoromethyl-41-chloro-anilide, -31 , 41-di-bromo-anilide, -31 , 41 , 51-trichloro-anilide, and -21 , 41 , 51-trichloro-anilide; 4-chlorosalicylic acid -31 , 41-dichloro-anilide, -31 , 41 , 51-trichloro-anilide, -21 , 41 , 51-trichloro-anilide, and -31-trifluoromethyl-41-chloro-anilide; 3.5-dichloro-salicylic acid -21 , 41 , 51-trichloro-anilide, -31 , 41 , 51-trichloro-anilide, -31-trifluoromethyl-41-chloro-anilide, and -21 , 31 , 41-trichloro-anilide; 3.5-dibromosalicylic acid -31 , 41-dichloro-anilide, and -31 , r1-dibromo-anilide; 3.5-di-iodosalicylic acid -31 , 41-dichloro-anilide, and -31 , 41 , 51-trichloro-anilide; 4 , 5-dichloro-salicylic acid -31 , 41-dichloro-anilide, -21 , 41 , 51-trichloro-anilide, -31 , 41 , 51-trichloro-anilide, -31-trifluoromethyl-41-chloro-anlide, -21 , 4-di-chloro-anilide, -21 , 51-dichloro-anilide, -41-chloro-anilide, -21 , 41-dibromo-anilide, -41-bromo-anilide, and -21 , 31 , 41trichloro-anilide; 4-methyl-5-chloro-salicylic acid-31 , 41-dichloro-anilide, -31 , 41 , 51-trichloro-anilide, and -31-trifluoromethyl-41-chloro-anilide; 5-bromo-salicylic acid-31 , 41-dichloro-anilide, -31 , 41 , 51-trichloro-anilide, and -21 , 31 , 41-trichloro-anilide; and salicylic acid -31 , 41 , 51-trichloro-anilide.